College of Veterinary Medicine, Hunan Agricultural University, Changsha, 410128, China.
Department of Laboratory Animal Science, Central South University, Changsha, 410013, China.
BMC Vet Res. 2024 May 10;20(1):187. doi: 10.1186/s12917-024-04052-5.
Porcine epidemic diarrhea virus (PEDV), a type of coronavirus, is one of the main pathogens that can infect pigs of all ages. It causes diarrhea and acute death of newborn piglets, resulting in massive economic losses to the worldwide swine industry. While vaccination remains the primary approach in combating PEDV, it often fails to address all the challenges posed by the infection, particularly in light of the emergence of evolving mutant strains. Therefore, there is a critical need to identify potent antiviral drugs that can effectively safeguard pigs against PEDV infection.
In this study, the antiviral efficacy of SP2509, a specific antagonist of Lysine-specific demethylase 1(LSD1), was evaluated in vitro. The RT-qPCR, Western blot, TCID and IFA showed that at a concentration of 1µmol/L, SP2509 significantly inhibited PEDV infection. Additionally, viral life cycle assays showed that SP2509 operates by impeding PEDV internalization and replication rather than attachment and release. Regarding mechanism, in Huh-7 cells, knockdowns LSD1 can suppress PEDV replication. This indicated that the inhibition effect of SP2509 on PEDV largely depends on the activity of its target protein, LSD1.
Our results in vitro show that SP2509 can inhibit PEDV infection during the internalization and replication stage and revealed a role of LSD1 as a restriction factor for PEDV. These imply that LSD1 might be a target for interfering with the viral infection, and SP2509 could be developed as an effective anti-PEDV agent.
猪流行性腹泻病毒（PEDV）是一种冠状病毒，是能够感染各年龄段猪的主要病原体之一。它会引起仔猪腹泻和急性死亡，给全球养猪业造成巨大的经济损失。虽然疫苗接种仍然是对抗 PEDV 的主要方法，但它往往无法应对感染带来的所有挑战，特别是在不断出现变异株的情况下。因此，迫切需要寻找能够有效保护猪免受 PEDV 感染的强效抗病毒药物。
本研究在体外评估了 LSD1 特异性拮抗剂 SP2509 的抗病毒功效。RT-qPCR、Western blot、TCID 和 IFA 结果表明，在 1µmol/L 的浓度下，SP2509 能显著抑制 PEDV 感染。此外，病毒生命周期实验表明，SP2509 通过阻碍 PEDV 的内化和复制而不是附着和释放来发挥作用。在 Huh-7 细胞中，LSD1 的敲低可以抑制 PEDV 的复制。这表明 SP2509 对 PEDV 的抑制作用在很大程度上取决于其靶蛋白 LSD1 的活性。
我们在体外的结果表明，SP2509 可以在 PEDV 的内化和复制阶段抑制 PEDV 感染，并揭示了 LSD1 作为 PEDV 限制因子的作用。这意味着 LSD1 可能是干扰病毒感染的靶点，而 SP2509 可能被开发为一种有效的抗 PEDV 药物。
